Desorption electrospray ionization (DESI) mass spectrometry, a versatile technique for analyzing small molecules, can now be used to analyze proteins and noncovalent protein complexes as large as 150 kilodaltons, chemists report (Anal. Chem., DOI: 10.1021/ac201390w). In conventional DESI, analytes are directly desorbed and ionized from a surface with an electrosprayed solvent. A newer version of DESI for analyzing liquid samples previously extended both the type of samples and the accessible mass range over the original version, but the technique still had not been used for large proteins and protein complexes, until now. Hao Chen of Ohio University, UCLA’s Joseph A. Loo, and coworkers showed that liquid-sample DESI is possible for proteins such as antibodies and noncovalent protein complexes such as manganese superoxide dismutase, a 46-kDa dimeric enzyme, and enolase, a 93-kDa dimeric enzyme. By changing the solvent composition, the researchers can adjust the charge state of the proteins without disrupting their structure and conformation, thus enabling the analysis of larger proteins and protein complexes.